This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The search for new strategies that can overcome the number of infectious diseases that have been developing drug-resistance, and new infectious diseases that could appear in the future, is a matter of major concern for public heath problems around the world. One of the approaches to fight this worldwide problem is the development of new therapeutic agents to face the challenge presented by drug-resistant microbes. Diseases such HIV infection, malaria and tuberculosis are the three major infections affecting humanity, and their control comprise the principal aims for world and national public health entities. Natural products chemistry can provide new drugs to face these problems, as has been the case in other eras of human history (i.e. Fleming discovery of penicillin). In recent years scientists from several fields of study, mainly medicinal-chemistry associated, have been attracted by the ability of fungi to produce secondary metabolites with diverse biological activities. Ecological habitats that have not been thoroughly investigated, such as Caribbean sea waters and Caribbean tropical plants, are good targets to search for undiscovered bioactive secondary metabolites. As an example, fungi living in highly saline tropical waters, or as endophites, in these environments could afford unprecedented chemical structures with activities against infectious diseases. Dr. Cantrell's laboratory at the Universidad del Turabo is currently conducting isolation of fungi from the Cabo Rojo solar salterns, at the Southwest of Puerto Rico. Dr. Cantrell and collaborators are also isolating endophitic fungi from the leaves of Coccoloba uvifera (sea grape), which grows along the coastal line, in sandy areas, and from mangrove trees of the Puerto Rico southeastern coast. Fungi from marine sediments are also the targets of Dr. Cantrell's Laboratory. These will be used for this research project. The specific aims of this project can be summarized as follows: - To evaluate the ability of fungal strains living in tropical marine environments, such as solar salterns, marine sediments, and mangrove trees around island of Puerto Rico for the production of bioactive secondary metabolites against malaria and tuberculosis. Previous to these tests, antifungal and antimicrobial properties will also be assayed. The search will also include endophitic fungi from the coastal tree Coccoloba uvifera (seagrape). - To separate the fungal strains possessing the ability to produce bioactive secondary metabolites into those corresponding to most widely studied species, and those belonging to less searched and to new species. - To use relatively large-scale culturing of less studied species showing the production of bioactive secondary metabolites, in order to make a chemical scrutiny of these strains, with the objective of test the bioactivity of individual compounds, identified by chromatographic and spectroscopic means. Since the structural diversity shown by fungi is very diverse 3, no structural specificity will be pursued, instead, we will seek for bioactivity at first glance, and then we will search for the structure responsible for that activity. - To test the isolated bioactive chemical compounds as anti-malarial and anti-tuberculosis agents.